Document Type
Article
Publication Title
PLoS ONE
Publication Date
9-1-2022
Volume
17
Issue
9 September
DOI
10.1371/journal.pone.0274675
Abstract
Glucocorticoids, such as dexamethasone (Dex), are used to prevent common side effects induced by chemotherapy and are heavily prescribed for solid cancers such as breast cancer. There is substantial pre-clinical data to support that Dex activation of the glucocorticoid receptor overrides chemotherapy-induced apoptosis in breast cancer cell lines. These findings are compounded by a recent study demonstrating that increased glucocorticoid receptor activation by endogenous stress hormones increased breast cancer heterogeneity and metastasis. Our study is the first to use both in vitro and in vivo models to thoroughly compare the Dex response on the migration of multiple estrogen receptor negative (ER-) and ER+ cancer cell lines. ER+ and ER-breast cancer cell lines were studied to compare their endogenous glucocorticoid activity as well as their metastatic ability in response to Dex treatment. We show that in the ER-breast cancer lines, Dex increases cell numbers, invasiveness, and migration, while decreasing apoptotic ability. Furthermore, we show that following Dex treatment, ER-breast cancer lines migrate further in an in vivo zebrafish model in comparison to ER+ cell lines. The use of ROR1 antibody to block WNT signaling diminished the metastatic properties of ER-cells, however recombinant WNT5A alone was not sufficient to induce migration. Taken together, we demonstrate that Dex treatment exacerbates the metastatic potential of ER-but not ER+ cells. These findings add to the growing body of data stressing the potential adverse role of endogenous and synthetic glucocorticoids in breast cancer biology.
E-ISSN
19326203
PubMed ID
36107918
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Crozier, Martin; Tubman, Janice; Fifield, Bre Anne; Ferraiuolo, Rosa Maria; Ritchie, Jenna; Zuccato, Katie; Mailloux, Emily; Sinha, Indrajit; Hamm, Caroline; and Porter, Lisa A.. (2022). Frequently used antiemetic agent dexamethasone enhances the metastatic behaviour of select breast cancer cells. PLoS ONE, 17 (9 September).
https://scholar.uwindsor.ca/biomedpub/7